Meteorological factors, air pollutants, and emergency department visits for otitis media: a time series study.

AbstractOtitis media (OM) is a very common disease in children, which results in a significant economic burden to the healthcare system for hospital-based outpatient departments, emergency departments (EDs), unscheduled medical examinations, and antibiotic prescriptions. The aim of this retrospective observational study is to investigate the association between climate variables, air pollutants, and OM visits observed in the 2007-2010 period at the ED of Cuneo, Italy. Measures of meteorological parameters (temperature, humidity, atmospheric pressure, wind) and outdoor air pollutants (particulate matter, ozone, nitrous dioxide) were analyzed at two statistical stages and in several specific steps (crude and adjusted models) according to Poisson's regression. Response variables included daily examinations for age groups 0-3, 0-6, and 0-18. Control variables included upper respiratory infections (URI), flu (FLU), and several calendar factors. A statistical procedure was implemented to capture any delayed effects. Results show a moderate association for temperature (T), age 0-3, and 0-6 with P < 0.05, as well as nitrous dioxide (NO2) with P < 0.005 at age 0-18. Results of subsequent models point out to URI as an important control variable. No statistical association was observed for other pollutants and meteorological variables. The dose-response models (DLNM-final stage) implemented separately on a daily and hourly basis point out to an association between temperature (daily model) and RR 1.44 at age 0-3, CI 1.11-1.88 (lag time 0-1 days) and RR 1.43, CI 1.05-1.94 (lag time 0-3 days). The hourly model confirms a specific dose-response effect for T with RR 1.20, CI 1.04-1.38 (lag time range from 0 to 11 to 0-15 h) and for NO2 with RR 1.03, CI 1.01-1.05 (lag time range from 0 to 8 to 0-15 h). These results support the hypothesis that the clinical context of URI may be an important risk factor in the onset of OM diagnosed at ED level. The study highlights the relevance of URI as a control variable to be included in the statistical analysis in association with meteorological factors and air pollutants. The study also points out to a moderate association of OM with low temperatures and NO2, with specific risk factors for this variable early in life. Further studies are needed to confirm these findings, particularly with respect to air pollutants in larger urban environments.

Beneficial effect of refined red palm oil on lipid peroxidation and monocyte tissue factor in HCV-related liver disease: a randomized controlled study.

BACKGROUND: A large amount of endotoxin can be detected in the peripheral venous blood of patients with liver cirrhosis, contributing to the pathogenesis of hepatotoxicity because of its role in oxidative stress. The present study aimed to test the effect of the supplementation with red palm oil (RPO), which is a natural oil obtained from oil palm fruit (Elaeis guineensis) rich in natural fat-soluble tocopherols, tocotrienols and carotenoids, on lipid peroxidation and endotoxemia with plasma endotoxin-inactivating capacity, proinflammatory cytokines profile, and monocyte tissue factor in patients with chronic liver disease. METHODS: The study group consisted of sixty patients (34 males and 26 females; mean age 62 years, range 54-75) with Child A/B, genotype 1 HCV-related cirrhosis without a history of ethanol consumption, randomly enrolled into an 8-week oral daily treatment with either vitamin E or RPO. All patients had undergone an upper gastrointestinal endoscopy 8 months before, and 13 out of them showed esophageal varices. RESULTS: Both treatments significantly decreased erythrocyte malondialdehyde and urinary isoprostane output, only RPO significantly affected macrophage-colony stimulating factor and monocyte tissue factor. Liver ultrasound imaging did not show any change. CONCLUSIONS: RPO beneficially modulates oxidative stress and, not least, downregulates macrophage/monocyte inflammatory parameters. RPO can be safely advised as a valuable nutritional implementation tool in the management of chronic liver diseases.

Association with meteo-climatological factors and daily emergency visits for renal colic and urinary calculi in Cuneo, Italy. A retrospective observational study, 2007-2010.

The incidence of nephrolithiasis is rising worldwide, especially in women and with increasing age. Incidence and prevalence of kidney stones are affected by genetic, nutritional, and environmental factors. The aim of this study is to investigate the link between various meteorological factors (independent variables) and the daily number of visits to the Emergency Department (ED of the S. Croce and Carle Hospital of Cuneo for renal colic (RC) and urinary stones (UC) as the dependent variable over the years 2007-2010.The Poisson generalized regression models (PGAMs) have been used in different progressive ways. The results of PGAMs (stage 1) adjusted for seasonal and calendar factors confirmed a significant correlation (p < 0.03) with the thermal parameter. Evaluation of the dose-response effect [PGAMs combined with distributed lags nonlinear models (DLNMs)-stage 2], expressed in terms of relative risk (RR) and cumulative relative risk (RRC), indicated a relative significant effect up to 15 lag days of lag (RR > 1), with a first peak after 5 days (lag ranges 0-1, 0-3, and 0-5) and a second weak peak observed along the 5-15 lag range days. The estimated RR for females was significant, mainly in the second and fourth age group considered (19-44 and >65 years): RR for total ED visits 1.27, confidence interval (CI) 1.11-1.46 (lag 0-5 days); RR 1.42, CI 1.01-2.01 (lag 0-10 days); and RR 1.35, CI 1.09-1.68 (lag 0-15 days). The research also indicated a moderate involvement of the thermal factor in the onset of RC caused by UC, exclusively in the female sex. Further studies will be necessary to confirm these results.

Testing a novel bioactive marine nutraceutical on osteoarthritis patients.

Osteoarthritis (OA) is a slow, chronic joint disease characterized by focal degeneration of articular cartilage and alterations of the chemical and mechanical articular function and also major cause of pain and physical disability. There is clinical evidence that increasing dietary n-3 relative to n-6 may be beneficial in terms of symptom management in humans but not all studies conclude that dietary n-3 PUFA supplementation is of benefit, in the treatment of OA. Our recent studies highlight the effect of a biomarine compound (LD-1227) on MMPs, collagen metabolism and on chondrocyte inflammatory markers. Thus, the aim of the present work was to test such bioactive compound versus a common nutraceutical intervention (glucosamine/chrondroitin sulfate) in knee osteoarthritis patients. The patients population consisted of 60 subjects with a recent diagnosis of knee osteoarthririts of mild-moderate severity. Patients were randomized in a double-blind study comparing LD-1227 (group A) versus a mixture of glucosamine (500 mg), chondroitin sulfate (400 mg) (group B). Patients were allowed their established painkillers on demand. At 4, 9 and 18 weeks patients were evaluated as for: VAS score assessing pain at rest, and during physical exercise, Lequesne index, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scale and KOOS scale. Moreover, serum concentrations of IL-6, IL-ß, CRP, TNF-sR1 and TNF-sR2 were assessed. As compared to GC treatment, LD-1227 yielded a quicker and higher degree of improvement of the whole clinical indexes and a lower NSAIDs use at the end of the study. LD-1227 brought about also a more significant downregulation of the tested cytokines cascade. Taken overall, these data suggest that LD-1227 has the potential to be included in the nutraceutical armamentarium in the management of OA.

A sturgeon-derived bioactive compound beneficially modulates nuclear receptors controlling metabolic functions in patients with metabolic syndrome.

The aim of the present study was to test the possible effects of a novel sturgeon-derived compound  (LD-1227) on inflammatory markers related to metabolic nuclear receptors in patients with metabolic syndrome. The study population consisted of 76 patients with metabolic syndrome and 30 healthy subjects who were maintained to their current treatments and randomly supplemented: A) LD-1227 (n=38) or B) placebo (n=38) as compared to C) healthy controls (n=30). LD-1227 or placebo (water-soluble starch) were given daily at breakfast and dinner for three months. Levels of hs-CRP, IL-6, TNF-α, leptin and adiponectin/ resistin index were assayed at the entry, 1 month and 3 months afterwards. At the end of the study period, as compared to B group, LD-1227-treated patients showed a significant improvement of all parameters tested, irrespective of the presence of diabetes. In particular, levels of adiponectin and adiponectin/ resistin index significantly increased following LD-1227 administration. Although the metabolic syndrome remains a multifaceted condition requiring a complex approach, LD-1227 could be a potential safe therapeutic tool to be integrated into a wider treatment and preventive medicine schedule strategy.

Mineral water inhalations for bronchial asthma: a meta-analysis.

Bronchial asthma (BA) is a common disease that contributes significantly to the incidence rate and death rate worldwide. A widespread treatment method is the use of inhalations of mineral waters, with conflicting information about their effectiveness. Purpose of the study was to assess the generalized effect power of the course of inhalations of mineral waters on the disease progress in patients with BA. A search of randomized clinical studies in data bases Pubmed, EMBASE, ELibrary, MedPilot amd CyberLeninka, according to PRISMA strategy, published between 1986 and July 2021. Standardized difference of mean values and their 95% of CI were employed for calculation using the random effects model. The meta-analysis drawing on 1266 sources included 14 studies, with 2 of them being randomized controlled clinical studies, including the results of the treatment of 525 patients. All 14 articles contain a conclusion that the inhalation of mineral water has a positive effect on the course of the disease in patients with BA. The analysis demonstrated that the group of patients after mineral water inhalations, compared with the control group, showed improvement of forced expiratory volume (FEV1), expressed both in % of the norm and in liters. The standardized difference of mean values FEV1 (%) (Hedge's g) was 8.2 (95% CI: 5.87 - 10.59; 100%), FEV1 values (liter.) (Hedge's g) was 0.69 (95% CI: -0.33-1.05). A significant heterogeneity of the results of individual studies was found (Q=124.96; tau2 = 14.55, I2 = 69.13%, p<0.0001 and Q=2.35; tau2 = 0, I2 = 0%, p<0.0001). Patients with mild, moderate, and hormone-dependent BA with a controlled and partially controlled disease course, after mineral water inhalations, compared with the control group, demonstrated a statistically significant decrease in the frequency and intensity of the cardinal symptoms of BA and improvement of FEV1.

Inhibiting insulin resistance mechanisms by DTS phytocompound: an experimental study on metabolic syndrome-prone adipocytes.

The present study was designed to determine whether DTS a phytocompound endowed with antioxidant properties, could beneficially modulate nitric oxide (NO) production stimulated by lipopolysaccharide (LPS) and tumor necrosis factor-alpha (TNF-alpha) in adipocytes. Combined stimulation (CS-treatment) exerted by using 5 microg/ml of LPS together with 100 ng/ml of TNF-alpha significantly enhanced NO production in 3T3-L1 adipocytes. Preincubation of the adipocytes with DTS (10-30 mM) inhibited such phenomenon in a dose-dependent fashion. The production of NO was decreased by 52% at the concentration of 30mM of DTS. The decrease in NO production by DTS was associated also with a decrease in inducible nitric oxide synthase (iNOS) protein and iNOS mRNA expression. Nuclear factor-kappa B (NF-kappaB) was significantly enhanced by CS-treatment, while the pretreatment with 30 mM of DTS prevented the activity by 27%. IL-6 production in 3T3-L1 adipocytes was markedly increased by CS stimulus, and the enhanced secretion of IL-6 was suppressed in a dose-dependent manner by DTS. These results suggest that DTS regulates iNOS expression and NO production in adipocytes through the modulating activation of NF-kappaB and may have a potential clinical application within protocols designed for treating metabolic syndrome. (www.actabiomedica.it).

Improving sperm quality and spermatogenesis through a bioactive marine compound: an experimental study.

Dietary lipids may affect sperm membrane structure, fluidity and its susceptibility to oxidative phenomena which may lead to altered sperm viability and proper binding to eggs. Given the recently demonstrated beneficial effects of fish oil diets on turkey fertility and embryo viability, the aim of this study was to test a caviar-derived marine product on spermatogenesis and sperm quality. Sixty mice were divided into four different groups and fed for 3 weeks with normal chow (group A), added with LD-1227 at the dosage of either 5 mg/day (B1) or 10 mg/day (B2) while Group C received standard chow added with 10 mg of a DHA-rich mixture. At sacrifice tests/body weight ration and spermatogenesis was checked. No toxicity, histological sign or body or testes growth abnormality was noted, irrespective of the treatment. As compared to control, all supplements showed to increase sperm counting and motility although the effect of LD-1227 10 mg was significantly higher than DHA alone (p<0.05). Viability was improved by DHA (p<0.05) but not by low LD-1227 dosage while higher dosage performed better than DHA (p<0.05). Morphology was unaffected by any of the employed supplements. Taken altogether, these data suggest that LD-1227 has a remarkable effect on quali-quantitative parameters of spermiogenesis, some of them being more effective than high dosage DHA. These findings may prove to be of interest in clinical practice. (www.actabiomedica.it).

Beneficial effect of a symbiotic preparation with S. boulardii lysate in mild stress-induced gut hyper-permeability.

Increased intestinal permeability has been advocated as one of the likely causes of various pathologies, such as allergies and metabolic or even cardiovascular disturbances. Thus, the aim of the present study was to test a symbiotic preparation containing microbial lysates (KC-1317, Named, Italy) against stress-induced derangement of gut mucosa permeability. Sprague Dawley rats were allocated into control (n=20) and stress (n=20) group. Stress was implemented by 1h of water avoidance stress daily for 10 days. Body weight, food and water intake and passage of stool pellet during stress session were recorded throughout the experiment. On the 11th day, fluorescent iso-thiocyanate dextran solution was injected into small intestinal loops. One hour after the injection, rats were sacrificed. Jejunum and ileum were taken for histopathology. Blood was collected from the abdominal aorta to measure intestinal permeability. In stress group, stool pellets during stress session was significantly higher than control group (p < 0.01). Villus height (p < 0.01), crypt depth (p < 0.01), number of goblet cells in villus (p < 0.01) and crypt (p < 0.05) decreased significantly in jejunum as compared to control. These phenomena were significantly prevented by KC-1317 (p < 0.05). Ileum also showed atrophy but villus height and the number of goblet cells in the villi did not significantly differ. Plasma-concentration of brain-gut peptides (substance P, thyrotropin-releasing hormone, cholecystokinin and motilin) were affected by stress (p < 0.001) and this effect did not change during supplementation with KC-1317. Polymorphonuclear neutrophil counting was significantly higher in stress group as compared to control (p < 0.01) but this phenomenon was abolished in the ileum (p < 0.01) or partly but significantly reduced by KC-1317 supplementation (p < 0.05). Accordingly, intestinal permeability was significantly enhanced in stress group as compared to control (p < 0.01) and prevented by KC-1317 (p < 0.01) in both intestinal segments examined. While confirming that chronic mild stress in rats compromises small intestinal morphology and permeability, we showed that a symbiotic microbial lysate can partly counteract this phenomenon.

Chemical composition and protective effect of oregano (Origanum heracleoticum L.) ethanolic extract on oxidative damage and on inhibition of NO in LPS-stimulated RAW 264.7 macrophages.

The present study shows the chemical profile and the in vitro properties (antioxidant and inhibition of nitric oxide production) of the Origanum heracleoticum L. (Lamiaceae). The ethanolic extract of the aerial parts is characterized by terpenes and fatty acids. The extract, with high total phenol and flavonoid content, showed a significant radical-scavenging activity (IC(50) value of 12.8 µg/mL) using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) test and an interesting antioxidant activity with the ß-carotene bleaching test (IC(50) values of 12.9 and 14.1 µg/mL at 30 and 60 min of incubation, respectively). The test for the inhibition of NO production, performed using the murine monocytic macrophage RAW 264.7 cell line, showed that the extract had significant activity with an IC(50) value of 108.5 µg/mL. The cytotoxic effect of O. heracleoticum extract in presence of lipopolysaccharide (LPS) (1 µg/mL) was evaluated but found to be negligible.

Correlation between environmental factors, chemical composition, and antioxidative properties of caper species growing wild in Calabria (South Italy).

Twenty samples of two caper species were collected from various natural habitats of Calabria (South Italy). A sample program was designed in order to cover all taxa and morphotypes present in the studied area, trying to correlate ecological conditions, phytochemical content, and biological activities. These species were characterized through the detection, isolation, and capillary GC-GC/MS quantitative evaluation of chemical markers (phytosterols and vitamin E). The antioxidant activity of MeOH caper extracts was assayed using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and ß-carotene bleaching tests. The chemical investigation showed a different composition according to the species and the populations. The best free radical (DPPH) scavenging activity was exerted by Capparis orientalis sample C4 (collected near Copanello village, granodiorite sea cliff) and Capparis sicula ssp. sicula sample C5 (collected near Tarsia village, clay soil). Sample C2 (Galatrella Valley, clay soil) showed the highest inhibition of linoleic acid oxidation with more efficacy than propyl gallate, the reference drug.

Hepatoprotective activity of a phytotherapeutic formula on thioacetamide--induced liver fibrosis model.

Hepatic fibrosis is a widespread alteration in the liver that primarily consists of increased collagen deposition in the tissue. The aim of the present study was to evaluate the protective effects of poly-phytocompound EH-1501 containing small amounts of silymarin but also other potentially effective substances on thioacetamide (TTA)-induced liver fibrosis and to elucidate the mechanisms underlying these protective effects in rats. Forty rats were randomly divided into four groups. Liver fibrosis was induced by intraperitoneal injection of 200 mg/kg body weight. TAA dissolved in saline was administered thrice a week, for 8 weeks. Groups 1 (normal healthy control) and 2 (liver injury model) received water for 8 weeks or silymarin (50 mg/kg p.o. daily) for 8 weeks (group 3) or a poly-phytocompound EH-1501 (containing grape leaf, wild strawberry, dandelion and milk thistle, EuroHealth, Italy) (200 mg/kg, daily respectively) for 8 weeks (group 4). Biochemistry and serum fibrosis markers were AST, ALT, GGT, bilirubin, thiobarbituric acid reactive substances (TBARs), hyaluronic acid and type IV collagen 7s. Liver tissue was used to assay glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD), TBARs, hydroxyproline and gene expression of collagen alpha1 (col alpha1) and transforming growth factor-beta1 (TGF-beta1). Silymarine and EH-1501 were equally effective in reducing serum markers of liver damage and fibrosis as well as oxidative stress. However, as compared to silymarine, EH-1501 was significantly more effective in improving tissue level of GPx while decreasing TBARs and hydroproline content (p < 0.05). When looking at gene expression of col alpha1 and TGF-beta1, EH-1501 showed a significantly higher degree of gene down-regulation as compared to silymarine (p < 0.05). Taken altogether, these data suggest that a natural antioxidant-containing phytocompound EH-1501 exerts an effective hepatoprotective property in experimental chronic fibrotizing liver injury to a significantly higher degree than silymarin.

Beneficial modification of functional renal parameters in 5/6 nephrectomized rats by nutraceutical. In view of a kidney-protective intervention.

The objective of this study is to ascertain the potential beneficial effects of a novel phytoterapeutic formula (DTS, Kyotsu Jigyo, Japan) on renal function and morphological structure in 5/6 nephrectomized rats. Male Spraque-Dawley rats, 240-280 g, were divided into sham control (Group A) and nephrectomized (Group B and Group C) groups. The 5/6 nephrectomy was performed by removal of the right kidney and 2/3 ligation of left renal artery. After surgery, the animals were kept in individual cage for 6 weeks. Rats in Group A and Group B were fed with a normal protein diet only while those in Group C were fed normal protein diet added with DTS (10 mg/rat/day). The DTS supplementation was started a day after surgery. After 5 weeks, all rats were subjected to renal function study and then their left kidneys were isolated for morphological study. There were no significant differences in body weight, blood pressure, and heart rate among groups. DTS supplementation significantly increased (p<0.05) plasma creatinine concentration, glomerular filtration rate, effective renal plasma flow, and urine flow rate in nephrectomized rats when compared to sham control (Group A) and untreated nephrectomized (Group B) controls. In contrast, plasma urea concentration and morphological structure were not significantly modified by DTS supplementation in nephrectomized animals. These data suggest that feeding with a normal protein diet and DTS supplementation improves renal function without any morphological effect in 5/6 nephrectomized rats if not a slight preservation.(www.actabiomedica.it).

Chelating, antioxidant and hypoglycaemic potential of Muscari comosum (L.) Mill. bulb extracts.

The metal chelating activity, antioxidant properties and the effect on carbohydrate-hydrolysing enzyme inhibition of Muscari comosum extracts have been investigated. M. comosum bulbs contain a total amount of the phenols with a value of 56.6 mg chlorogenic acid equivalent per gram of extract and a flavonoid content of 23.4 mg quercetin equivalent per gram of extract. In order to evaluate the non-polar constituents, n-hexane extract was obtained. Gas chromatography-mass spectrometry analysis revealed the presence of fatty acids and ethyl esters as major constituents, with different aldehydes and alkanes as minor components. Ethanolic extract had the highest ferric-reducing ability power (66.7 µM Fe(II)/g) and DPPH scavenging activity with a concentration giving 50% inhibition (IC50) value of 40.9 µg/ml. Moreover, this extract exhibited a good hypoglycaemic activity with IC50 values of 81.3 and 112.8 µg/ml for α-amylase and α-glucosidase, respectively. In conclusion, M. comosum bulbs show promising antioxidant and hypoglycaemic activity via the inhibition of carbohydrate digestive enzymes. These activities may be of interest from a functional point of view and for the revalorization of this ancient non-cultivated vegetable of Mediterranean traditional gastronomy.

Balneotherapy and hydrotherapy in chronic respiratory disease.

Chronic respiratory diseases (CRD) belong to major noncommunicable diseases (NCD) targeted by World Health Organization (WHO) NCD Action Plan and United Nations (UN) Sustainable Development Goal (STG) 3.4 to achieve 30% decline of mortality by the year 2030. Strong evidence is now available in the literature for therapeutic aquatic exercise interventions in improving health status of chronic obstructive pulmonary diseases (COPD) patients. However, gym-based exercises can be difficult for patients with COPD who are mainly elderly and often have co-morbidities-such as severe arthritis and obesity-which may impair their ability to exercise at an adequate intensity. Besides improving respiratory function and health status in COPD, exercise in water helps overcoming patient's fears and promote socialization, contrasting the risk of depression, which is a major condition often associated with long term COPD condition. Susceptibility to respiratory infections plays a role in exacerbations of COPD. Sulphur-rich water inhalations improve muco-ciliary clearance, reduce inflammatory cytokines production and inflammatory mucosal infiltration, reduce elastase secretion by neutrophils, preserving elastic properties of pulmonary interstitium and thus facilitating expectoration. Repeated cold water stimulations in COPD also reduce frequency of infections. Finally, sauna bathing reduces the risk of pneumonia. On the other side, hydrotherapy/balneotherapy also help obesity control, which is one of the most difficult NCD risk factors to modify and consequently is an important component of the WHO preventive strategy to achieve STG 3.4. Along with high prevalence and mortality, CRD cause increasing pharmaceutical and hospital costs. In this perspective, Health Resort Medicine should not be ignored as a resource in the WHO NCD strategy and Universal Health Coverage, providing a multi-stakeholder platform (including the network of health resorts and their facilities) able to give a real help to the achievement of UN goal STG 3.4 by the year 2030.

Short-term air pollution exposure is a risk factor for acute coronary syndromes in an urban area with low annual pollution rates: Results from a retrospective observational study (2011-2015).

BACKGROUND: Epidemiological data suggest that air pollutants are risk factors for cardiovascular disease. Recent studies have questioned the adequacy of current legal pollutant limits, because concentrations lower than those recommended still affect cardiovascular morbidity and mortality. AIM: To investigate the association between short-term exposure to air pollutants and the daily diagnosis of acute coronary syndrome (ACS) at the emergency department (ED) of S. Croce Hospital (Cuneo, Italy), between 2011 and 2015. METHODS: We evaluated the effect of particulate matter (PM2.5-10), nitrogen dioxide and ozone as primary exposure, together with temperature and relative humidity as climatological control variables, on ED admissions for ACS (response variables). We studied residents aged ≥35 years, classified into three age groups (35-64, 65-74 and ≥75 years). Environmental data were analysed according to Poisson's regression, and conventional cardiovascular risk factors (CRFs; hypertension, diabetes, coronary artery disease, smoking and dyslipidaemia) were included as control variables. RESULTS: ED admissions for ACS were 1625/391,689, with 298 in 2011 (0.183%), 305 in 2012 (0.188%), 347 in 2013 (0.214%), 341 in 2014 (0.21%) and 334 in 2015 (0.206%), with a general growth rate of 2.08% (from 2011 to 2015). The CRFs examined were confirmed to be highly associated with occurrence of ACS. Our study identified PM2.5 and temperature in all age groups to be additional risk factors, with PM2.5 exposure (P<0.01) being a particular risk for those aged ≥75 years. Dose-response models confirmed only PM2.5 as the main environmental risk factor in elderly patients (relative risk 1.06, 95% confidence interval 1.02-1.11; lag time 0-3 days). We also found a consistent relative risk for temperature in all age groups. CONCLUSION: This study confirms the importance of PM2.5 as a risk factor for ACS, mostly in elderly patients, even in a city with low annual pollution rates.

Low dose oral administration of cytokines for treatment of allergic asthma.

Many inflammatory diseases are characterized by an imbalance among lymphocyte populations, in particular Th1, Th2 and the recently described Th17 cells. The Th1/Th2 imbalance is linked to many factors, but certainly the role of cytokines is essential. In Th2 diseases IL-4 expression is predominant, while Th1 pathologies are characterized by high expression of IFN-gamma and IL-12. Though today the therapeutical proposal for many inflammatory diseases aims to re-establish normal levels of Th1/Th2 cytokines, the pharmacological use of cytokines, which are very active molecules, is limited by the possible collateral effects. Therefore, our study aims to determine, in a murine model of allergic asthma, the possible therapeutic activity of low dose cytokines solutions, mechanically activated. We found that oral administration of low doses IL-12 plus IFN-gamma is able to solve the bronchial hyperresponsiveness condition of mice, establishing normal cytokine levels. The anti-asthma activity was confirmed by histological analysis of lungs and broncho-alveolar lavage fluid cell count. Serum ovalbumin-specific IgE was also significantly inhibited by treatment with low dose activated cytokines solution. These findings may suggest a novel approach to diseases which involve a Th1/Th2 imbalance.

A 2-year Double-Blind RCT Follow-up Study with Fermented Papaya Preparation (FPP) Modulating Key Markers in Middle-Age Subjects with Clustered Neurodegenerative Disease-Risk Factors.

In recent years a number of studies have reported the significant relationship between metabolic syndrome and neurodegenerative disease. There is accumulating evidence that the interplay of combined genetic and environmental risk factors (from diet to life style to pollutants) to intrinsic age-related oxi-inflammatory changes may be advocated for to explain the pandemic of neurodegenerative diseases. In recent years a specific Fermented Papaya Preparation (FPP) has been shown to significantly affect a number of redox signalling abnormalities in a variety of chronic diseases and as well in aging mechanisms either on experimental and on clinical ground. The aim of the present study was to evaluate FPP use in impending metabolic disease patients with potentially neurodegenerative disease clustered risk factors. The study population consisted of 90 patients aged 45-65 years old, with impending metabolic syndrome and previously selected as to be ApoE4 genotype negative. By applying a RCT, double-blind method, one group received FPP 4.5 g twice a day (the most common dosage utilized in prior clinical studies) while the other received an oral antioxidant cocktail (trans-resveratrol, selenium, vitamin E, vitamin C). Then, after 21 month treatment period, a selected heavy metal chelator was added at the dosage of 3 g/nocte for the final 3 months study treatment. The parameters tested were: routine tests oxidized LDL-cholesterol, anti-oxidised LDL, Cyclophilin-A (CyPA), plasminogen activator inhibitor-1 and CyPA gene expression. From this study it would appear that FPP, unlike the control antioxidant, significantly decreased oxidized-LDL and near normalizing the anti-Ox-LDL/Ox-LDL ratio (p<0.001) although unaffecting the lipid profile per sè. Moreover, only FPP decreased cyclophilin-A plasma level and plasminogen activator-inhibitor (p<0.01) together with downregulating cyclophilin-A gene expression (p<0.01). Insulin resistance was only mildly improved. Heavy metals gut clearance proved to be effectively enhanced by the chelator (p<0.01) and this was not affected by any of the nutraceuticals, nor it added any further benefit to the biological action of FPP.

Occlusion, sternocleidomastoid muscle activity, and body sway: a pilot study in male astronauts.

The modifications induced by microgravity on the coordinated patterns of movement of the head, trunk, and limbs are reported on extensively. However, apparently there is little data on the masticatory muscles. In normal gravitational conditions, information from the neck and stomatognathic apparatus play a role in maintaining the body's balance and equilibrium. The current pilot study used normal gravity conditions to investigate the hypothesis of a functional coupling between occlusion and neck muscles and body postural oscillations. The immediate effect of modified occlusal surfaces on the contraction pattern of the sternocleidomastoid muscles during maximum voluntary clenching and on the oscillation of the center of foot pressure was analyzed in 11 male astronauts (aged 31-54 yrs). All subjects were healthy and free from pathologies of the neck and stomatognathic apparatus. Occlusal splints were prepared using impressions of their dental arches. The splints were modeled on the mandibular arch, had only posterior contacts, and were modified to obtain a more symmetric, standardized contraction of the masseter and temporalis muscles during teeth clenching. Surface EMG activity of the sternocleidomastoid muscles was recorded during a maximal voluntary clench with and without the splint. Sternocleidomastoid potentials were standardized as percent of the mean potentials recorded during a maximum contralateral rotation of the head, and the symmetry of the EMG waves of left- and right-side muscles was measured. Body sway was assessed with and without the splint, either with eyes open or closed. The variations of the center of foot pressure were analyzed through bivariate analysis, and the area of the 90% standard ellipse was computed. Within each visual condition (eyes open or closed), the difference between the areas of oscillation measured with and without the splint was computed. Muscular activity was more symmetric with the splint. The area of oscillation of the center of foot pressure was larger without the splint than with the splint, both with eyes open and eyes closed. The modifications, induced by the occlusal splint in the sternocleidomastoid muscles' symmetry, and center of foot pressure differential area with closed eyes, were significantly related (p < 0.05): the larger the increment in muscular symmetry, the smaller the area of oscillation with the splint as compared to without the splint. A functionally more symmetric maxillo-mandibular position resulted in a more symmetric sternocleidomastoid muscle contraction pattern and less body sway. Modifications in the contraction of the masticatory muscles may therefore affect the whole body.

Oral Administration of Interleukin-10 and Anti-IL-1 Antibody Ameliorates Experimental Intestinal Inflammation.

BACKGROUND: To elucidate the effects of a solution containing interleukin-10 and anti-IL-1 antibody in modulating experimental intestinal inflammation. METHODS: Colitis was induced in BALB/c mice by oral administration of dextran sodium sulphate; mice were then treated with interleukin-10 plus anti-IL-1 antibody at low dosage. Transepithelial electrical resistance of isolated mouse colon and colon lengths were evaluated. Cytokines concentrations in organocultures supernatants and plasma samples were evaluated by Enzyme-Linked Immuno Sorbent Assay. Tight junction proteins were evaluated by immunofluorescence, respectively. RESULTS: Oral administration of tested products restores intestinal barrier function during experimental intestinal inflammation in association with reduced levels of proinflammatory cytokines, increased interleukin-10 plasma concentrations and a tight junction architecture restoration. CONCLUSION: Obtained results may contribute to modelling an interesting strategy for the treatment of patients with inflammatory bowel diseases.